People with Autism Have Lower Levels of a Key Endocannabinoid

What the researchers found

Blood anandamide (AEA) levels were significantly lower in individuals with ASD (SMD=-0.79, p=0.002) compared to controls. In animal models, hippocampal AEA was also significantly decreased (SMD=-1.06, p<0.01), and prefrontal cortex 2-AG was reduced (SMD=-1.00, p=0.04). Narrative synthesis found that elevating AEA and 2-AG levels improved core autistic-like symptoms in animal models, with region- and sex-dependent variations.

Why it matters

If endocannabinoid deficiency contributes to autism symptoms, targeted therapies that raise endocannabinoid levels (such as FAAH inhibitors or potentially CBD) could represent a novel treatment approach.

The numbers in context

Blood AEA in humans with ASD: SMD=-0.79 (95% CI: -1.28 to -0.30, p=0.002). Hippocampal AEA in animal models: SMD=-1.06 (95% CI: -1.78 to -0.33, p<0.01). Prefrontal cortex 2-AG: SMD=-1.00 (95% CI: -1.93 to -0.06, p=0.04). 47 papers assessed, 21 included.

How the study worked

Systematic review and meta-analysis of 16 animal studies and 5 human studies on endocannabinoid system alterations in ASD. Random-effects meta-analysis for quantitative synthesis.

What this study cannot tell us

Only 5 human studies available. High heterogeneity in some analyses. Animal models of autism may not fully reflect human ASD. Blood endocannabinoid levels may not reflect brain levels. Various ASD models and species used across studies.

How to read the evidence

Meta-analysis with consistent findings across human and animal data, but limited by small number of human studies and high heterogeneity.

When this study was published

2025 publication.

The bigger picture

The endocannabinoid system regulates social behavior, emotional processing, and sensory integration, all of which are affected in autism. These findings provide biological plausibility for the growing interest in cannabinoid-based interventions for ASD.

Questions still open

• Could FAAH inhibitors that raise anandamide levels improve autism symptoms in clinical trials?
• Do endocannabinoid levels predict which individuals with ASD might respond to cannabinoid-based treatments?

Read the original research

Alterations of the endocannabinoid system in autism spectrum disorder: a systematic review and meta-analysis.

European archives of psychiatry and clinical neuroscience, 275(8), 2493-2509

Citation

Jia, Xinlei; Gao, Shumin; Liu, Xiaotong; Feng, Zhendong; Wang, Xingxing; Lan, Kunyi; Lu, Yan'e; Han, Lei; Wei, Ya Bin; Liu, Jia Jia. (2025). Alterations of the endocannabinoid system in autism spectrum disorder: a systematic review and meta-analysis.. European archives of psychiatry and clinical neuroscience, 275(8), 2493-2509. https://doi.org/10.1007/s00406-025-02031-x

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